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LOCALIZATION

NEUROLOGY

EPISODE IIIPERIPHERAL NEUROPATHY

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DISEASE of PERIPHERAL NERVE

� LMN weakness in distribution of

peripheral nerves, or distal > proximal

� Sensory loss in distribution of peripheral

nerves or distal distribution

� Hyporeflexia

� Disturbance of autonomic nervous system

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CLASSIFICATION

� MONONEURITIS SIMPLEX

� MONONEURITIS MULTIPLEX

� POLYNEUROPATHY

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Mononeuritis Simplex

Involve 1 nerve in 1 time

eg. Bell’s palsy, Entrapment, Radiculopathy

Mononeuritis Multiplex

Involve 1 nerve in 1 time but additive

eg. Vasculitic neuropathy

Polyneuropathy

Involve many nerves in the same time

eg. GBS, CIDP

NEUROPATHY

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Mononeuropathy

Simplex

Polyneuropathy

Axonal type

Mononeuropathy

Multiplex

NEUROPATHY

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DEMYELINATION

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DEMYELINATION

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POLYNEUROPATHY

AXONOPATHY

� Distal sensory loss (glove and stocking pattern)

� Distal weakness, leg > arm

� Loss of distal DTR > proximal DTR

� Length dependent

Bilateral symmetrical distal weakness

and sensory loss

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� Metabolic disease: DM

� Toxic substance, drugs, alcohol

� Vitamin deficiency : B1, B6

� Vasculitis

� Infectious: HIV, Hepatitis

� Paraneoplastic Syndrome

� Monoclonal gammopathy

� Rare: hereditary, amyloidosis

AXONOPATHY

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Alcohol

Amiodarone

Dapsone (motor)

Disulfuram

Hydralazine

INH

Metronidazole

Nitrofurantoin

ARV

Phenytoin

Pyridoxine (sensory)

Vincristine

Taxol

Arsenic

Thallium

Organophosfate

Lead (motor)

Hydrocarbon

Hydrocarbon

Amiodarone

Perhexiline

DEMYELINATING

POLYNEUROPHY

AXONAL

POLYNEUROPATHY

toxic

AXONAL

POLYNEUROPATHY

drug

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� Not length dependent

� Proximal and distal weakness

� Distal sensory loss little

(not in length dependent)

� Generalized absent or decreased reflexes

Bilateral symmetrical or asymmetrical distal

weakness without sensory loss

POLYNEUROPATHY

DEMYELINATION

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ACQUIRE

� AIDP

(Acute Inflammatory Demyelinating Polyneuropathy)

� CIDP

(Chronic Inflammatory Demyelinating Polyneuropathy)

� MMN

(Multifocal Motor Neuropathy with conduction block)

� Drug (amiodarone)

DEMYELINATION

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CONGENITAL

� HNPP (Hereditary Neuropathy with Labiality to Pressure Palsy)

� CMT(Charchot-Marine-Tooth) (HMSN)

DEMYELINATION

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AIDP : GBS and its variants

� AIDP anti GD1a (65%)

� AMAN anti GM1 (C. jujuni), anti GD1a

(acute motor axonal neuropathy)

� AMSAN anti GM1 (C. jujuni), anti GD1a

(acute motor sensory axonal neuropathy

� Miller-Fischer variant anti GQ1b (Ab to cerebellar layer)

� Pure Autonomic

DEMYELINATION

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CIDP : clinical as AIDP but progress more than

4 weeks anti-MAG (myelin associated glycoprotein)

associated with systemic diseases

� Monoclonal gammopathy (MGUS)

� Multiple myeloma

� Waldenstromm macroglobulinemia

� Cryoglobulinemia

� Osteosclerotic myeloma (POEMS)

� Infections eg. Hepatitis B, Hepatitis C, HIV

DEMYELINATION

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� Lead neuropathy

Predominantly involve upper extremities

Wrist drop

� Dapsone

� Multifocal motor neuropathy with

conduction blocks (MMN)

Middle age male, distal upper extremities,

hand atrophy, chronic course

DDx from ALS

DEMYELINATION

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ENLARGE NERVE

� Leprosy

� CIDP

� Genetic: CMT, HNPP

NEUROPATHY with FACIAL INVOLVEMENT

� GBS

� CIDP (rare)

� Lyme disease

� Sarcoidosis

ADDITIONAL CLUE

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� ACUTE

GBS, Porphyria, Diphtheria

� CHRONIC

CIDP

� VERY CHRONIC

Hereditary neuropathy (CMT)

ADDITIONAL CLUE

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MONONEURITIS MULTIPLEX

� Multiple nerve in multiple time

� Many nerve = polyneuropathy

� 3 major cause

1. Idiopathic

2. Autoimmune disease and vasculitis

3. Paraneoplastic syndrome

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VASCULITIS

� Vasculitic syndrome:

Wegener granulomatosis,

Churg-Strauss syndrome, PAN

� Systemic connective tissue disease: SLE, RA

� Other vasculitis:

� Cryoglobulinemia, Hepatitis B, Heptitis C

MONONEURITIS MULTIPLEX

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� Entrapment syndrome

eg. CTS, Saturday night palsy

� Ulnar nerve palsy

� Nerve ischemia : DM

� Infection : Leprosy, Ramsay Hunt

� Idiopathic : Bell’s palsy

MONONEURITIS SIMPLEX

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APPROACH to NEUROPATHY

polyneuropathymononeuropathy

simplex

mononeuropathy

multiplex

• entrapment

• idiopathic

• vasculitis

• paraneoplastics

• idiopathicdemeyelination axonopathy

acutechronic

AIDP and

varients

• CIDP

• lead

• CMT (HMSN)

• HNPP

• drug (cordarone)

• Metabolic disease: DM

• Toxic substance, drugs

• Vitamin deficiency : B1, B6

• Vasculitis

• Infectious: HIV, Hepatitis

• Paraneoplastic Syndrome

• Monoclonal gammopathy

• Rare: hereditary, amyloidosis

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APPROACH to NEUROPATHY

� Duration

� Function

• Motor nerves

• Sensory nerves

• Motor and sensory nerves

• Autonomic nerves

• Small fiber sensory nerves

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APPROACH to NEUROPATHY

� Proximal or distal

� Symmetrical or asymmetrical

� Distal DTR loss or loss all DTR

� Nerve enlargement

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� Systemic disease: DM, thyroid

� Toxic substance: heavy metal

� Drug: CMT, ARV

� Alcoholic drinking

� Nutritional deficiency

� Autoimmune disease: PAN, Wegener

� Family history: CMT

� Infectious disease: leprosy, HBV, HCV,

HIV, HSV

APPROACH to NEUROPATHY

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GUILLIAN BARRE’S SYNDROME

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peripheral polyneuropathy

demyelination in nature (but axonal involve can occur)

GBS

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isolated condition (post infectious disorder)

not associated with systemic disease, autoimmune

infectious condition URI (40%), diarrhea (27%)

2/3 have anticedent infection (three weeks before)

post vaccination, post surgical, stress event

pathogen

- CMV, EBV, M. pneumoniae, H. influinzae, HIV

- Campylobactor jejuni

GBS

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PATHOPHYSIOLOGY

infection with pathogen

antigen and antibody complex

antibody to myelin

complement activation

demyelination

involve axon (severe)

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VARIANT and ANTIBODY

AIDP Unknown

AMAN GM1, GM1b, GD1a, GalNAc-GD1a

AMSAN GM1, GM1b, GD1a, GalNAc-GD1a

MFS GQ1b, GT1a, GD3

Pure Dysautonomia

AIDP = acute inflammatory demyelinating polyradiculoneuropathy

AMAN = acute motor axonal neuropathy

AMSAN = acute motor sensory axonal neuropathy

MFS = Miller-Fischer syndrome

Variant Antibody

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rapidly progressive bilateral weakness

relatively symmetrical

distal and proximal weakness

involve cranial muscle (facial)

MFS = ocular muscle

triad (ataxia, areflexia, ophthalmoplegia)

decrease or absent DTR

involve respiratory muscle (25%)

reach to maximum within 4 weeks (mostly 2 weeks)

CLINICAL PROFILES

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INVESTIGATIONS

Lumbar Puncture

increase protein content but normal WBC

call “albuminocytodissociation”

may be normal in first week but 90% abnormal in second week

increase cell = carcinomatosis, HIV, lymphoma

Electrodiagnostic Test

demyelination pattern (decrease velocity)

may be normal in first week

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CLINICAL PROFILES

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Require for diagnosis

Progressive weakness both arms and legs (start in the leg)

Decrease or absent DTR

GBS DIAGNOSIS

Support diagnosis

Progressive over day to 4 weeks

Relative symmetry of symptoms

Mild sensory symptoms

Cranial muscle involvement (bifacial weakness)

Autonomic dysfunction

Pain

High concentration of CSF protein

Typical electrodiagnostic features

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Doubt about diagnosis

Severe pulmonary dysfunction with limited limb weakness

Severe sensory signs or sharp sensory level

Bladder/bowel dysfunction at onset

Mark persistent asymmetrical weakness

Increase CSF cell count (> 50) or PMN in CSF

GBS DIAGNOSIS

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intracranial/cord abnormalities

- brain stem encephalitis

- meningitis carcinomatosis/lymphomatosis

- transverse myelitis

- cord compression

DIFFERENTIAL DIAGNOSIS

Peripheral nerve abnormalities

- CIDP

- porphyria

- critical illness neuropathy

- Beri beri

Neuromuscular junction and muscle abnormalities

- MG, botulinum toxin

- polymyositis/dermatomyositis

- critical illness myopathy

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common complication (2/3)

cardiac arrhythmia (3-10%)

blood pressure fluctuation

sweating

pupillary abnormality

bowel/bladder dysfunction

AUTONOMIC FAILURES

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HUGHES’S SEVERITY SCORE

MEANING

1 Minor signs or symptoms

2 Able to walk 5 meters without assistance

3 Able to walk 5 meters with the help of one

person or stick

4 Unable to walk or wheelchair

5 Require assisted ventilation

6 Death

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TREATMENT

supportive treatment/PTPlasma exchange (severity score ≥ 3)

Intravenous immunoglobulin (IVIg) 0.4 g/kg/d five days

oral steroid and/or methylprednisolone not effective

20% dependent walk at 6 months

Data limit

- after 2 weeks of disease- mild symptoms (severity score ≤ 2)

- pediatrics

- MFS